title: Description of a riboflavin biosynthetic gene variant prevalent in the phylum Proteobacteria.
abstract: Riboflavin (vitamin B2) is the precursor of flavin mononucleotide and flavin adenine dinucleotide, which are cofactors essential for a host of intracellular redox reactions. Microorganisms synthesize flavins de novo to fulfill nutritional requirements, but it is becoming increasingly clear that flavins play a wider role in cellular physiology than was previously appreciated. Flavins mediate diverse processes beyond the cytoplasmic membrane, including iron acquisition, extracellular respiration, and interspecies interactions. While investigating the regulation of flavin electron shuttle biosynthesis in the Gram-negative gammaproteobacterium Shewanella oneidensis, we discovered that a riboflavin biosynthetic gene (ribBA) annotated as encoding a bifunctional 3,4-dihydroxy-2-butanone 4-phosphate (DHBP) synthase/GTP cyclohydrolase II does not possess both functions. The novel gene, renamed ribBX here, encodes an amino-terminal DHBP synthase domain. The carboxy-terminal end of RibBX not only lacks GTP cyclohydrolase II activity but also has evolved a different function altogether in S. oneidensis, regulating the activity of the DHBP synthase domain. Phylogenetic analysis revealed that the misannotation of ribBX as ribBA is rampant throughout the phylum Proteobacteria (40% of 2,173 annotated ribBA genes) and that ribBX emerged early in the evolution of this group of microorganisms. We examined the functionality of representative ribBX genes from Beta-, Gamma-, and Epsilonproteobacteria and found that, consistent with sequence-based predictions, the encoded GTP cyclohydrolase II domains lack catalytic activity. The persistence of ribBX in the genomes of so many phylogenetically divergent bacterial species lends weight to the argument that ribBX has evolved a function which lends a selective advantage to the host.
authors.affiliation: BioTechnology Institute.
authors.forename: Evan D
authors.initials: ED
authors.lastname: Brutinel
authors.forename: Antony M
authors.initials: AM
authors.lastname: Dean
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gralnick
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics*; D019143:Evolution, Molecular; D019751:Intramolecular Transferases / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D020560:Proteobacteria / Q000201:enzymology* / Q000235:genetics*; D012256:Riboflavin / Q000096:biosynthesis*; D017386:Sequence Homology, Amino Acid
chemical_list: D019751:Intramolecular Transferases; C066493:L-3,4-dihydroxy-2-butanone-4-phosphate synthase; D012256:Riboflavin